Displaying publications 81 - 100 of 6739 in total

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  1. Functionalized Carbon Nano-scale Drug Delivery Systems From Biowaste Sago Bark For Cancer Cell Imaging
    Abdul Manaf SA, Hegde G, Mandal UK, Wui TW, Roy P
    Curr Drug Deliv, 2017;14(8):1071-1077.
    PMID: 27745545 DOI: 10.2174/1567201813666161017130612
    BACKGROUND: Nano-scale carbon systems are emerging alternatives in drug delivery and bioimaging applications of which they gradually replace the quantum dots characterized by toxic heavy metal content in the latter application.

    OBJECTIVE: The work intended to use carbon nanospheres synthesized from biowaste Sago bark for cancer cell imaging applications.

    METHODS: This study synthesised carbon nanospheres from biowaste Sago bark using a catalyst-free pyrolysis technique. The nanospheres were functionalized with fluorescent dye coumarin-6 for cell imaging. Fluorescent nanosytems were characterized by field emission scanning electron microscopy-energy dispersive X ray, photon correlation spectroscopy and fourier transform infrared spectroscopy techniques.

    RESULTS: The average size of carbon nanospheres ranged between 30 and 40 nm with zeta potential of -26.8 ± 1.87 mV. The percentage viability of cancer cells on exposure to nanospheres varied from 91- 89 % for N2a cells and 90-85 % for A-375 cells respectively. Speedy uptake of the fluorescent nanospheres in both N2a and A-375 cells was observed within two hours of exposure.

    CONCLUSION: Novel fluorescent carbon nanosystem design following waste-to-wealth approach exhibited promising potential in cancer cell imaging applications.

    Matched MeSH terms: Carbon/pharmacology*; Fluorescent Dyes/pharmacology*
  2. Effects of oil substrate supplementation on production of prodigiosin by Serratia nematodiphila for dye-sensitized solar cell
    Abdul Manas NH, Chong LY, Tesfamariam YM, Zulkharnain A, Mahmud H, Abang Mahmod DS, et al.
    J Biotechnol, 2020 Jun 20;317:16-26.
    PMID: 32348830 DOI: 10.1016/j.jbiotec.2020.04.011
    Bacterial pigments are potential substitute of chemical photosensitizer for dye-sensitized solar cell (DSSC) due to its non-toxic property and cost-effective production from microbial fermentation. Serratia nematodiphila YO1 was isolated from waterfall in Malaysia and identified using 16S ribosomal RNA. Characterization of the red pigment produced by the bacteria has confirmed the pigment as prodigiosin. Prodigiosin was produced from the fermentation of the bacteria in the presence of different oil substrates. Palm oil exhibited the best performance of cell growth and equivalent prodigiosin yield compared to olive oil and peanut oil. Prodigiosin produced with palm oil supplementation was 93 mg/l compared to 7.8 mg/l produced without supplementation, which recorded 11.9 times improvement. Specific growth rate of the cells improved 1.4 times when palm oil was supplemented in the medium. The prodigiosin pigment produced showed comparable performance as a DSSC sensitizer by displaying an open circuit voltage of 336.1 mV and a maximum short circuit current of 0.098 mV/cm2. This study stands a novelty in proving that the production of prodigiosin is favorable in the presence of palm oil substrate with high saturated fat content, which has not been studied before. This is also among the first bacterial prodigiosin tested as photosensitizer for DSSC application.
    Matched MeSH terms: Culture Media/pharmacology
  3. Fulltext Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats
    Abdul Nasir NA, Agarwal R, Sheikh Abdul Kadir SH, Vasudevan S, Tripathy M, Iezhitsa I, et al.
    PLoS One, 2017;12(3):e0174542.
    PMID: 28350848 DOI: 10.1371/journal.pone.0174542
    Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress. These effects of tocotrienol invlove reduced NFκB activation, lower iNOS expression, restoration of ATP level, ATPase activities, calpain activity and lens protein levels.
    Matched MeSH terms: Antioxidants/pharmacology; Tocotrienols/pharmacology*
  4. Effects of topically applied tocotrienol on cataractogenesis and lens redox status in galactosemic rats
    Abdul Nasir NA, Agarwal R, Vasudevan S, Tripathy M, Alyautdin R, Ismail NM
    Mol Vis, 2014;20:822-35.
    PMID: 24940038
    Oxidative and nitrosative stress underlies cataractogenesis, and therefore, various antioxidants have been investigated for anticataract properties. Several vitamin E analogs have also been studied for anticataract effects due to their antioxidant properties; however, the anticataract properties of tocotrienols have not been investigated. In this study, we investigated the effects of topically applied tocotrienol on the onset and progression of cataract and lenticular oxidative and nitrosative stress in galactosemic rats.
    Matched MeSH terms: Tocotrienols/pharmacology
  5. Microwave-assisted synthesis of sec/tert-butyl 2-arylbenzimidazoles and their unexpected antiproliferative activity towards ER negative breast cancer cells
    Abdul Rahim AS, Salhimi SM, Arumugam N, Pin LC, Yee NS, Muttiah NN, et al.
    J Enzyme Inhib Med Chem, 2013 Dec;28(6):1255-60.
    PMID: 23061895 DOI: 10.3109/14756366.2012.729828
    A new series of N-sec/tert-butyl 2-arylbenzimidazole derivatives was synthesised in 85-96% yields within 2-3.5 min by condensing ethyl 3-amino-4-butylamino benzoate with various substituted metabisulfite adducts of benzaldehyde under focused microwave irradiation. The benzimidazole analogues were characterised using (1)H NMR, (13)C NMR, high resolution MS and melting points. Evaluation of antiproliferative activity of the benzimidazole analogues against MCF-7 and MDA-MB-231 revealed several compounds with unexpected selective inhibitions of MDA-MB-231 in micromolar range. All analogues were found inactive towards MCF-7. The most potent inhibition against MDA-MB-231 human breast cancer cell line came from the unsubstituted 2-phenylbenzimidazole 10a.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Benzimidazoles/pharmacology*
  6. Behavioral and cortisol analysis of the anti-stress effect of Polygonum minus (Huds) extracts in chronic unpredictable stress (CUS) zebrafish model
    Abdul Rahim N, Nordin N, Ahmad Rasedi NIS, Mohd Kauli FS, Wan Ibrahim WN, Zakaria F
    Comp Biochem Physiol C Toxicol Pharmacol, 2022 Jun;256:109303.
    PMID: 35202824 DOI: 10.1016/j.cbpc.2022.109303
    The World Health Organization (WHO) recorded approximately 350 million people worldwide have suffered from mental health disorders, such as depression, anxiety, schizophrenia, and addictive behaviors. The search for new drugs from nature has drawn on many biological resources and human practices. In this study, leaves of Polygonum minus standardized extract (Biokesum®), 1 and 100 mg/L were used to evaluate the anti-stress effect in the chronic unpredictable stress (CUS) zebrafish model. Five groups of zebrafish were manipulated in this study, comprising control, chronic unpredictable stress (CUS), CUS + Biokesum® 1 mg/L (4 days, 20 min/day, immersion) CUS + Biokesum® 100 mg/L (4 days, 20 min/day, immersion) and CUS + fluoxetine 0.6 mg/L (4 days, 20 min/day, immersion). Four different behavioral tests were used, i.e. open-field test, social interaction test, light and dark test, and exploratory test. After four consecutive days of treatment, the zebrafish were sacrificed for whole-body cortisol analysis. The exploratory test showed a significant change upon P. minus treatment (one-way ANOVA; p = 0.0011). Cortisol analysis showed a decrease of cortisol level after treatment with the extract and fluoxetine, without significant difference. These results showed that zebrafish is a reliable model to study the anti-stress effect of compounds or herbal extract.
    Matched MeSH terms: Fluoxetine/pharmacology; Plant Extracts/pharmacology
  7. Fulltext Recent Advances in Nanoencapsulation Systems Using PLGA of Bioactive Phenolics for Protection against Chronic Diseases
    Abdul Rahim R, Jayusman PA, Muhammad N, Ahmad F, Mokhtar N, Naina Mohamed I, et al.
    Int J Environ Res Public Health, 2019 Dec 06;16(24).
    PMID: 31817699 DOI: 10.3390/ijerph16244962
    Plant-derived polyphenolic compounds have gained widespread recognition as remarkable nutraceuticals for the prevention and treatment of various disorders, such as cardiovascular, neurodegenerative, diabetes, osteoporosis, and neoplastic diseases. Evidence from the epidemiological studies has suggested the association between long-term consumption of diets rich in polyphenols and protection against chronic diseases. Nevertheless, the applications of these phytochemicals are limited due to its low solubility, low bioavailability, instability, and degradability by in vivo and in vitro conditions. Therefore, in recent years, newer approaches have been attempted to solve the restrictions related to their delivery system. Nanoencapsulation of phenolic compounds with biopolymeric nanoparticles could be a promising strategy for protection and effective delivery of phenolics. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers that has attracted considerable attention due to its attractive properties. In this review, our main goal is to cover the relevant recent studies that explore the pharmaceutical significance and therapeutic superiority of the advance delivery systems of phenolic compounds using PLGA-based nanoparticles. A summary of the recent studies implementing encapsulation techniques applied to polyphenolic compounds from plants confirmed that nanoencapsulation with PLGA nanoparticles is a promising approach to potentialize their therapeutic activity.
    Matched MeSH terms: Phenols/pharmacology*
  8. Fulltext Potential Antioxidant and Anti-Inflammatory Effects of Spilanthes acmella and Its Health Beneficial Effects: A Review
    Abdul Rahim R, Jayusman PA, Muhammad N, Mohamed N, Lim V, Ahmad NH, et al.
    Int J Environ Res Public Health, 2021 Mar 29;18(7).
    PMID: 33805420 DOI: 10.3390/ijerph18073532
    Oxidative stress and inflammation are two common risk factors of various life-threatening disease pathogenesis. In recent years, medicinal plants that possess antioxidant and anti-inflammatory activities were extensively studied for their potential role in treating and preventing diseases. Spilanthes acmella (S. acmella), which has been traditionally used to treat toothache in Malaysia, contains various active metabolites responsible for its anti-inflammatory, antiseptic, and anesthetic bioactivities. These bioactivities were attributed to bioactive compounds, such as phenolic, flavonoids, and alkamides. The review focused on the summarization of in vitro and in vivo experimental reports on the antioxidant and anti-inflammatory actions of S. acmella, as well as how they contributed to potential health benefits in lowering the risk of diseases that were related to oxidative stress. The molecular mechanism of S. acmella in reducing oxidative stress and inflammatory targets, such as inducible nitric oxide synthase (iNOS), transcription factors of the nuclear factor-κB family (NF-κB), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) signaling pathways were discussed. Besides, the antioxidant potential of S. acmella was measured by total phenolic content (TPC), total flavonid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and superoxide anion radical scavenging (SOD) and thiobarbituric acid reactive substance (TBARS) assays. This review revealed that S. acmella might have a potential role as a reservoir of bioactive agents contributing to the observed antioxidant, anti-inflammatory, and health beneficial effects.
    Matched MeSH terms: Anti-Inflammatory Agents/pharmacology; Antioxidants/pharmacology; Plant Extracts/pharmacology
  9. The effect of selected plant extracts on the development of single-species dental biofilms
    Abdul Rahim ZH, Shaikh S, Hasnor Wan Ismail WN, Wan Harun WH, Razak FA
    J Coll Physicians Surg Pak, 2014 Nov;24(11):796-801.
    PMID: 25404435 DOI: 11.2014/JCPSP.796801
    To determine the effect of a mixture of plant extracts on the adherence and retention of bacteria in dental biofilm.
    Matched MeSH terms: Anti-Infective Agents/pharmacology*; Plant Extracts/pharmacology*; Thymol/pharmacology*
  10. Fulltext Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells
    Abdul Rahman A, Jamal AR, Harun R, Mohd Mokhtar N, Wan Ngah WZ
    BMC Complement Altern Med, 2014;14:213.
    PMID: 24980711 DOI: 10.1186/1472-6882-14-213
    Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment.
    Matched MeSH terms: Antineoplastic Combined Chemotherapy Protocols/pharmacology*; Chromans/pharmacology*; Eugenol/pharmacology; Vitamin E/pharmacology
  11. Transcriptome analysis reveals the molecular mechanisms of combined gamma-tocotrienol and hydroxychavicol in preventing the proliferation of 1321N1, SW1783, and LN18 glioma cancer cells
    Abdul Rahman A, Mokhtar NM, Harun R, Jamal R, Wan Ngah WZ
    J Physiol Biochem, 2019 Nov;75(4):499-517.
    PMID: 31414341 DOI: 10.1007/s13105-019-00699-z
    Gamma-tocotrienol (GTT) and hydroxychavicol (HC) exhibit anticancer activity in glioma cancer cells, where the combination of GTT + HC was shown to be more effective than single agent. The aim of this study was to determine the effect of GTT + HC by measuring the cell cycle progression, migration, invasion, and colony formation of glioma cancer cells and elucidating the changes in gene expression mitigated by GTT + HC that are critical to the chemoprevention of glioma cell lines 1321N1 (grade II), SW1783 (grade III), and LN18 (grade IV) using high-throughput RNA sequencing (RNA-seq). Results of gene expression levels and alternative splicing transcripts were validated by qPCR. Exposure of glioma cancer cells to GTT + HC for 24 h promotes cell cycle arrest at G2M and S phases and inhibits cell migration, invasion, and colony formation of glioma cancer cells. The differential gene expression induced by GTT + HC clustered into response to endoplasmic reticulum (ER) stress, cell cycle regulations, apoptosis, cell migration/invasion, cell growth, and DNA repair. Subnetwork analysis of genes altered by GTT + HC revealed central genes, ATF4 and XBP1. The modulation of EIF2AK3, EDN1, and FOXM1 were unique to 1321N1, while CSF1, KLF4, and FGF2 were unique to SW1783. PLK2 and EIF3A gene expressions were only altered in LN18. Moreover, GTT + HC treatment dynamically altered transcripts and alternative splicing expression. GTT + HC showed therapeutic potential against glioma cancer as evident by the inhibition of cell cycle progression, migration, invasion, and colony formation of glioma cancer cells, as well as the changes in gene expression profiles with key targets in ER unfolded protein response pathway, apoptosis, cell cycle, and migration/invasion.
    Matched MeSH terms: Antineoplastic Agents/pharmacology; Chromans/pharmacology*; Eugenol/pharmacology; Vitamin E/pharmacology
  12. Fulltext Targeting the B-cell lymphoma 2 anti-apoptotic proteins for cervical cancer treatment
    Abdul Rahman SF, Xiang Lian BS, Mohana-Kumaran N
    Future Oncol, 2020 Oct;16(28):2235-2249.
    PMID: 32715755 DOI: 10.2217/fon-2020-0389
    The B-cell lymphoma 2 (BCL-2) anti-apoptotic proteins have become attractive therapeutic targets especially with the development of BH3-mimetics which selectively target these proteins. However, it is important to note that expression levels of the anti-apoptotic proteins and their relevance in inhibiting apoptosis varies between different cell lineages. This addiction to certain anti-apoptotic proteins for survival, can be determined with various techniques and targeted effectively with selective BH3-mimetics. Studies have highlighted that anti-apoptotic proteins BCL-XL and MCL-1 are crucial for cervical cancer cell survival. Co-targeting BCL-XL and MCL-1 with selective BH3-mimetics yielded promising results in cervical cancer cell lines. In this review, we focus on the expression levels of the anti-apoptotic proteins in cervical cancer tissues and how to possibly target them with BH3-mimetics.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*
  13. Fulltext Gamma-tocotrienol treatment increased peroxiredoxin-4 expression in HepG2 liver cancer cell line
    Abdul Rahman Sazli F, Jubri Z, Abdul Rahman M, Karsani SA, Md Top AG, Wan Ngah WZ
    BMC Complement Altern Med, 2015;15:64.
    PMID: 25886747 DOI: 10.1186/s12906-015-0590-y
    To determine the antiproliferative effect of gamma-tocotrienol (GTT) treatment on differential protein expression in HepG2 cells.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Antioxidants/pharmacology*; Vitamins/pharmacology; Tocotrienols/pharmacology*
  14. Fulltext Synergistic Roles of Curcumin in Sensitising the Cisplatin Effect on a Cancer Stem Cell-Like Population Derived from Non-Small Cell Lung Cancer Cell Lines
    Abdul Satar N, Ismail MN, Yahaya BH
    Molecules, 2021 Feb 18;26(4).
    PMID: 33670440 DOI: 10.3390/molecules26041056
    Cancer stem cells (CSCs) represent a small subpopulation within a tumour. These cells possess stem cell-like properties but also initiate resistance to cytotoxic agents, which contributes to cancer relapse. Natural compounds such as curcumin that contain high amounts of polyphenols can have a chemosensitivity effect that sensitises CSCs to cytotoxic agents such as cisplatin. This study was designed to investigate the efficacy of curcumin as a chemo-sensitiser in CSCs subpopulation of non-small cell lung cancer (NSCLC) using the lung cancer adenocarcinoma human alveolar basal epithelial cells A549 and H2170. The ability of curcumin to sensitise lung CSCs to cisplatin was determined by evaluating stemness characteristics, including proliferation activity, colony formation, and spheroid formation of cells treated with curcumin alone, cisplatin alone, or the combination of both at 24, 48, and 72 h. The mRNA level of genes involved in stemness was analysed using quantitative real-time polymerase chain reaction. Liquid chromatography-mass spectrometry was used to evaluate the effect of curcumin on the CSC niche. A combined treatment of A549 subpopulations with curcumin reduced cellular proliferation activity at all time points. Curcumin significantly (p < 0.001) suppressed colonies formation by 50% and shrank the spheroids in CSC subpopulations, indicating inhibition of their self-renewal capability. This effect also was manifested by the down-regulation of SOX2, NANOG, and KLF4. Curcumin also regulated the niche of CSCs by inhibiting chemoresistance proteins, aldehyde dehydrogenase, metastasis, angiogenesis, and proliferation of cancer-related proteins. These results show the potential of using curcumin as a therapeutic approach for targeting CSC subpopulations in non-small cell lung cancer.
    Matched MeSH terms: Cisplatin/pharmacology*; Curcumin/pharmacology*
  15. Uterotrophic, fetotoxic and abortifacient effect of a Malaysian variety of Plumbago rosea L. on isolated rat uterus and pregnant mice
    Abdul Sattar M, Abdullah NA, Khan MA, Dewa A, Samshia D
    Pak J Biol Sci, 2007 Mar 01;10(5):763-7.
    PMID: 19069860
    Traditionally Plumbago rosea L. is used as an abortifacient in the Southeast Asian region. Methanolic root extract of a local species of Plumbago rosea L. was studied to evaluate its traditional antifertility claim. Interestingly, it was found to possess dose related inhibitory effect on uterine contractile responses elicited by oxytocic agents on isolated uteri of pregnant and pseudo-pregnant rats. Furthermore, it was found to possess significant (p < 0.05) fetotoxic activity along with mild abortive potential in pregnant mice when given orally at high doses (400 and 800 mg kg(-1)) once daily for ten days starting from day 10 of gestation. The results derived indicated possible presence of utero-active compound (s) in this plant that inhibited oxytocic agents induced uterine motility. Moreover, pronounced fetotoxic and mild abortifacient potentials observed at higher doses in pregnant mice might support its accredited traditional use to avoid unwanted pregnancy.
    Matched MeSH terms: Abortifacient Agents/pharmacology*; Plant Extracts/pharmacology*
  16. Nutritional values and bioactive components of under-utilised vegetables consumed by indigenous people in Malaysia
    Abdul Wahab N, Ahdan R, Ahmad Aufa Z, Kong KW, Johar MH, Shariff Mohd Z, et al.
    J Sci Food Agric, 2015 Oct;95(13):2704-11.
    PMID: 25410129 DOI: 10.1002/jsfa.7006
    Diverse plants species in the forest remain under-utilised and they are mainly consumed only by local people. However, increasing issues in food security prompted the present study, which explores the nutritional and antioxidant aspects of Malaysian under-utilised vegetables. The studied vegetables were Paku Nyai (Stenochlaena palustris), Cemperai (Champereia manillana), Maman Pasir (Cleome viscose), Dudung (Erechtites valerianifolia) and Semambuk (Ardisia pendula).
    Matched MeSH terms: Antioxidants/pharmacology*; Ascorbic Acid/pharmacology*; Flavonoids/pharmacology; Phenols/pharmacology; Plant Extracts/pharmacology; beta Carotene/pharmacology*; Polyphenols/pharmacology*
  17. Natural cholinesterase inhibitors from Myristica cinnamomea King
    Abdul Wahab SM, Sivasothy Y, Liew SY, Litaudon M, Mohamad J, Awang K
    Bioorg Med Chem Lett, 2016 08 01;26(15):3785-92.
    PMID: 27236720 DOI: 10.1016/j.bmcl.2016.05.046
    A new acylphenol, malabaricone E (1) together with the known malabaricones A-C (2-4), maingayones A and B (5 and 6) and maingayic acid B (7) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 3 (1.84±0.19 and 1.76±0.21μM, respectively) and 4 (1.94±0.27 and 2.80±0.49μM, respectively) were identified as dual inhibitors, with almost equal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibiting potentials. The Lineweaver-Burk plots of compounds 3 and 4 indicated that they were mixed-mode inhibitors. Based on the molecular docking studies, compounds 3 and 4 interacted with the peripheral anionic site (PAS), the catalytic triad and the oxyanion hole of the AChE. As for the BChE, while compound 3 interacted with the PAS, the catalytic triad and the oxyanion hole, compound 4 only interacted with the catalytic triad and the oxyanion hole.
    Matched MeSH terms: Biological Products/pharmacology*; Cholinesterase Inhibitors/pharmacology*
  18. Immunosuppressive Effects of Annona muricata L. Leaf Extract on Cellular and Humoral Immune Responses in Male Wistar Rats
    Abdul Wahab SM, Husain K, Jantan I, Arshad L, Haque MA, Mohd Fauzi N, et al.
    Curr Pharm Biotechnol, 2023;24(11):1465-1477.
    PMID: 36545731 DOI: 10.2174/1389201024666221221113020
    BACKGROUND: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation.

    OBJECTIVE: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses.

    METHODS: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days.

    RESULTS: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4+ and CD8+ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH).

    CONCLUSION: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.

    Matched MeSH terms: Plant Extracts/pharmacology
  19. Mangiferin (mango) attenuates AOM-induced colorectal cancer in rat's colon by augmentation of apoptotic proteins and antioxidant mechanisms
    Abdul-Aziz Ahmed K, Jabbar AAJ, Abdulla MA, Zuhair Alamri Z, Ain Salehen N, Abdel Aziz Ibrahim I, et al.
    Sci Rep, 2024 Jan 08;14(1):813.
    PMID: 38191592 DOI: 10.1038/s41598-023-50947-y
    Mangiferin (MF) is a natural C-glucosylxantone compound that has many substantial curative potentials against numerous illnesses including cancers. The present study's goal is to appraise the chemo preventive possessions of MF on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) in rats. Rats clustered into 5 groups, negative control (A), inoculated subcutaneously with normal saline twice and nourished on 0.5% CMC; groups B-E injected twice with 15 mg/kg azoxymethane followed by ingestion of 0.5% CMC (B, cancer control); intraperitoneal inoculation of 35 mg/kg 5-fluorouracil (C, reference rats) or nourished on 30 mg/kg (D) and 60 mg/kg (E) of MF. Results of gross morphology of colorectal specimens showed significantly lower total colonic ACF incidence in MF-treated rats than that of cancer controls. The colon tissue examination of cancer control rats showed increased ACF availability with bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands compared to MF-treated rats. Mangiferin treatment caused increased regulation of pro-apoptotic (increased Bax) proteins and reduced the β-catenin) proteins expression. Moreover, rats fed on MF had significantly higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lower malondialdehyde (MDA) concentrations in their colonic tissue homogenates. Mangiferin supplementation significantly down-shifted pro-inflammatory cytokines (transforming growth factor-α and interleukine-6) and up-shifted anti-inflammatory cytokines (interleukine-10) based on serum analysis. The chemo-protective mechanistic of MF against AOM-induced ACF, shown by lower ACF values and colon tissue penetration, could be correlated with its positive modulation of apoptotic cascade, antioxidant enzymes, and inflammatory cytokines originating from AOM oxidative stress insults.
    Matched MeSH terms: Antioxidants/pharmacology
  20. Fulltext Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit
    Abdul-Aziz MH, Abd Rahman AN, Mat-Nor MB, Sulaiman H, Wallis SC, Lipman J, et al.
    Antimicrob Agents Chemother, 2016 01;60(1):206-14.
    PMID: 26482304 DOI: 10.1128/AAC.01543-15
    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Carbapenems/pharmacology
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